The long-term objective of this work is to develop improved methods for identifying and characterizing large molecules, and to apply these methods to various biological problems. Time-of-flight (TOF) techniques will be used to determine the mass spectra of ions ejected from organic compounds by electrospray. (SIMS), and by laser desorption (LDMS), as well as ions produced by electrospray. Structural information about the sample molecules will be obtained from the normal mass spectra and from the measurement of correlations between neutral and charged daughters in a reflecting TOF spectrometer. These measurements will be made in three time-of-flight mass spectrometers constructed in our laboratory: 1) linear spectrometer (TOFI); 2) a reflecting instrument (TOFII), which gives improved resolution and enables measurement of correlations between neutral and charged fragments; 3) a second reflecting instrument (TOFIII), not yet in full operation, which will be modified for use with an electrospray ion source. The laboratory possesses a versatile laser system, built by Lumonics; it consists of a high repetition rate excimer laser with gas purifier, a tuneable dye laser, and a frequency doubler. A small nitrogen laser is also available. The lasers will be used for laser desorption and for experiments on ion dissociation after acceleration. Specifically it is proposed: 1. To make improvements in instrumentation and technique. The use of an I- ion source (already constructed) for desorption will be investigated. Laser desorption will be carried out on the reflecting instrument (TOFII) with the hope of obtaining improved resolution. An electrospray ion source will be installed in TOF III. 2. To carry out studies on the basic physics of laser desorption, secondary ion emission, particle detection and ion dissociation, so as to obtain a better understanding of these processes and to facilitate their application to biological problems. The emission of electrons and secondary ions from various struck by large molecules will be investigated. 3. To apply time-of-flight mass spectrometry to various samples of biological interest, in particular to peptides, proteins and nucleotides.